https://www.medrxiv.org/conten….20117929v1.full.pdf+html

Propensity score (PS) weighted Kaplan-Meier plot demonstrated a survival advantage (57% vs. 25%) at 35 days from admission to the ICU in patients who received therapeutic anticoagulation for a minimum of 5 days compared to those who received prophylactic anticoagulation during their hospital course. A multivariate Cox proportional hazard regression model with PS weights to adjust for baseline differences found a 79% reduction in death in patients who were therapeutically anticoagulated HR 0.209, [95% CI (0.10, 0.46), p <0.001]. Bleeding complications were similar between both groups. A 26.7% [95% CI (1.16, 1.39), p<0.001] excess mortality was found for each 1 mg/dL rise in serum creatinine over a 21-day period. Conclusions: Therapeutic anticoagulation is associated with a survival advantage among patients with COVID-19 who require mechanical ventilation in the ICU.

A therapy that works?

Large reduction in deaths if this observational study holds. It may not, but it is a carefully caveated and apolitical preprint.

Quote from stefan

What about this study of HCQ

Always read the limitations

"Even though the study used the gold standard methodology of conducting clinical research, outside researchers saw significant limitations. The study was conducted in an unusual way: over the internet, without patients being seen by study doctors.

Maybe the WHO has something conclusive in 10 days time..

Quote from stefan

No, it's not made by humans, unless we are talking about state sponsored multi billion project to kill a good part of the world including your own people.

There has been bio-weapon research in the past. As far as I know, all states (nations) stopped doing it years ago. I suppose China might be doing it secretly. But here is the thing about bio-weapons: you always make one with an antidote or vaccine, to protect your own military forces. For example, you weaponize anthrax, which has a vaccine. Then you inoculate all of your own soldiers with the vaccine, and you loose the virus on the enemy army or civilian population. No nation would develop a bio-weapon with no cure. It would destroy your own army as quickly as the enemy's. In this case, it destroyed the Chinese economy as readily as any other. The Chinese leaders are a ruthless dictatorship, but dictators do not want to wreck their own economy.

People have speculated the rogue terrorists might develop and deploy a bio-weapon with no antidote. However, the lab this one supposedly came from is not operated by a terrorist organization. Say what you like about the Chinese government, it definitely wants to preserve the status quo. It happens there was an editorial about this very subject today, written by the former ambassador to China from India (not an American):

https://www.nytimes.com/2020/0…erica-united-nations.html

China Doesn’t Want a New World Order. It Wants This One.

Why would China go to the trouble of capsizing the global order when it can simply take it over?

Quote from RobertBryant

Always read the limitations

"Even though the study used the gold standard methodology of conducting clinical research, outside researchers saw significant limitations. The study was conducted in an unusual way: over the internet, without patients being seen by study doctors.

Maybe the WHO has something conclusive in 10 days time..

All studies have limitations. There may be more lack of compliance etc here, but it was randomised controlled. I don't see much of a problem doing it over the internet unless you think people were deliberately spoofing it.

I doubt anything will be conclusive, all studies just small increments of fallible evidence.

Quote from THHuxleynew

And here is your answer: from RmYN02 - a virus newly isolated from bats

Quote from THHuxleynew

anti-Chinese sentiment makes the "escaped from Chinese lab" hypothesis popular, and it is difficult to disprove. But it does not seem likely.

I did not know how naive you are! 93% match. Mutation-rate of a virus is at best one base/week. Now you can start to calculate and finally ask the question how likely this is....

It has nothing to do with anti Chinese moods. This kind of ruthless research is done in the US too. There is only one difference: Chinese labs have no experience and are more eager to get funds/publications from underpaid staff than in other places.

Of course the Chinese will try hard to reinsert the CoV-9 virus into a bat. But this will be extremely difficult because of the human optimizations/add-ons they introduced. Do not expect a fitting bat virus within the next 6 months. But this will certainly happen as predicted - may with the help of US folks....

Quote from THHuxleynew

Neither the bat betacoronaviruses nor the
pangolin betacoronaviruses sampled thus
far have polybasic cleavage sites

No longer true? As my last post. A relatively short read.

No. It still is true. While the RmYN02 virus has an insertion between the two spike protein sequences, it is NOT polybasic. It does not resemble at all the polybasic insertion sequence of SARS CoV-2. So the spike proteins on RmYN02 are not Furin cleavable, cannot enter human cells are of no harm to humans.

Quote from THHuxleynew

All studies have limitations

All studies have limitations,,? another THHist truism

Here is a Vioxx-ist addon ... " but some have more limitations than others...some lethal".

One might hope that after Surgisphere both the NEJM and Lancet might call a hold on rushing stuff into print.

"

Steven Nissen, a cardiologist and veteran clinical trialist at the Cleveland Clinic, was much harsher.

The fact that patients self-reported their data

and that one in five did not take all their doses of the study drug

, as well as the study’s small size

, made him less than confident that the study could entirely rule out that hydroxychloroquine had some preventative effect

. He emphasized that more studies of the drug, which was widely prescribed during the initial months of the Covid-19 pandemic, have not been completed

.

“Absence of evidence is not evidence of absence,”

. “Poor quality data does not help it only confuses the world.

That’s exactly where we find ourselves, in a state of confusion.”

David Boulware, a professor of medicine at the University of Minnesota Medical School, said he thought up the study

, which was also far cheaper to run than a conventional clinical trial

, precisely because he saw a need to get something done with minimal resources

Maybe sub-minimal? The study was too underpowered to decide anything... and just added to the HCQ-fog

Quote from RobertBryant

The study was too underpowered to decide anything

The calculation of the power of the study is fraught with error.

Often a small pilot study is run beforehand ...which takes at least several months

to get some idea of the variability.

Even if you do this .. you can end up with a study that is underpowered..

not many journals like .."Oops! my study was underpowered"

then there is common tendency to eliminate the discrepant 'noise'

by deleting some of the input data..

Been there...done that..

It might take at least another 6 months to get some sensible HCQ data.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3256489/

Very fishy.

https://science.thewire.in/the…tional-study-surgisphere/

Why That Observational Study of Hydroxychloroquine in The Lancet Seems Fishy

HCQ appears to be still working for the Mumbai India police force -

"Toll climbs to 9, cops on HCQS spared the worst" (Times of India)

http://timesofindia.indiatimes…m=text&utm_campaign=cppst

Video from Peak Properity - Too Much Damage Is Being Done By The Bungled Response To Covid-19

- HCQ works in India - cites this paper in the Indian Journal of Medical Research --

"Healthcare workers & SARS-CoV-2 infection in India: A case-control investigation in the time of COVID-19"

http://www.ijmr.org.in/preprintarticle.asp?id=285520;type=0

- Peak Prosperity also references the small, but successful Lebanese study

"Previous RC trials of antivirals have been underpowered( n too small)

according to Japanese(mainly) statistical study..

if treatment is initiated more than 12 hours after symptoms start.".

This grossly simplifies their paper... sumimasen

Rethinking antiviral effects for COVID-19 in clinical studies:

early initiation is key to successful treatment

https://www.medrxiv.org/conten…05.30.20118067v1.full.pdf

"We first quantified the heterogeneity of viral dynamics which could be a confounder...

Second, we demonstrated that a drug is unlikely to be effective if initiated after a short period following symptom onset.

For accurate evaluation of the efficacy of an antiviral drug for COVID-19

, antiviral treatment should be initiated before or soon after symptom onset in RCTs.

The fact that patients self-reported their data

and that one in five did not take all their doses of the study drug

, as well as the study’s small size

, made him less than confident that the study could entirely rule out that hydroxychloroquine had some preventative effect

. He emphasized that more studies of the drug, which was widely prescribed during the initial months of the Covid-19 pandemic, have not been completed

We are agreed then. No study can entirely rule anything out! In fact this guy is being a lot more positive in his evaluation of the results than me. I am saying that study is just one more brick of (negative re prophylaxis) evidence to add to the overall picture. No way definitive.

Quote from RobertBryant

“Absence of evidence is not evidence of absence,”

. “Poor quality data does not help it only confuses the world.

That’s exactly where we find ourselves, in a state of confusion.”

RB - now you are posting what I have been saying all along. All the data we have now, positive and negative, is poor.

The difficult issue is that faced with many deaths and maybe hospitals over-run, doctors can accept prescribing based on poor data if balance of risk versus reward seems good.

The HCQ debate is just that, for political reasons, the matter was publicly highlighted, and correct evaluation of the (very early) data was pre-empted, so that as more (also poor) data came in doctors are criticised for making sensible decisions to hold off general use. Blame Trump - a pretty easy call.

One of the differences between science and politics is that scientists are allowed (in fact required) to change their minds based on new evidence. In this case the evidence is so poor it is difficult to say whether you do good or harm by treating with HCQ. Enough positives for trials in some circumstances. Different doctors will reach different conclusions. No-one should be criticised for exercising judgement either way in such a marginal situation.

THH

Quote from Wyttenbach

I did not know how naive you are! 93% match. Mutation-rate of a virus is at best one base/week. Now you can start to calculate and finally ask the question how likely this is....

Ever heard of insertion and recombination? or looked at the table (in my other link) of matching of different critical subsequences? In any case the significance of that virus is as below. Read on...

Quote from Mark U

No. It still is true. While the RmYN02 virus has an insertion between the two spike protein sequences, it is NOT polybasic. It does not resemble at all the polybasic insertion sequence of SARS CoV-2. So the spike proteins on RmYN02 are not Furin cleavable, cannot enter human cells are of no harm to humans.

This post (validated by two others liking it). Makes me go check the polybasic Furin cleavage argument again. Maybe Mark U is right and all those biologists are wrong? It was not as simplistic as supposed above, if you read the link I provided, which I bet mark U did not. However, I read it very quickly, so let's do a more detailed review...

https://www.virology.ws/2020/0…arginine)%20amino%20acids

The figure shows amino acids at cleavage sites in the spike glycoproteins of various CoVs. A furin site is present in the spike glycoprotein of HCoV-OC43, HCoV-HKU1, MERS-CoV and SARS-CoV 2. It is called a multibasic site because it contains multiple basic (arginine) amino acids. The spike glycoproteins of HCoV-NL63, HCoV-229E, and SARS-CoV do not contain this multibasic cleavage site. Neither do SARS-related CoVs found in bats, including RaTG13, the virus with the closest overall genome sequence identity with SARS-CoV-2.

An interesting question is the origin of the furin cleavage site it SARS-CoV-2. Its closest relative, the bat isolate RaTG13, does not have this site. Nor do any of the other bat SARS-like CoVs or the pangolin CoVs that have been isolated. However recently a newly isolated bat SARS-like CoV, RmYN02, was shown to contain a poly basic amino acid insertion in the spike glycoprotein. This observation supports the hypothesis that the furin cleavage site in SARS-CoV-2 arose by recombination among bat viruses in nature.

So the link is this: polybasic amino acid insertions happen naturally in bat viruses. Therefore the polybasic Furin cleavage site found in sars-cov-2 is an expected natural occurrence in bat viruses. Contrary to the "it must have come from a lab" argument.

Zhou et al. report a bat-derived coronavirus, RmYN02, which is the closest relative of SARS-CoV-2 in most of the virus genome reported to date. RmYN02 contains an insertion at the S1/S2 cleavage site in the spike protein in a similar manner to SARS-CoV-2. This suggests that such insertion events can occur naturally in animal betacoronaviruses.

THH

The scientists think the wuhan lab idea is rubbish, so do the spooks.

https://www.thetimes.co.uk/art…ame-from-market-mghqw3bxr

Ordinarily, if scientists want to be critical of a colleague’s work they might call it “interesting”. Or, the most damning verdict of all, “brave” (Tom Whipple writes).

Kristian Andersen, an immunologist at the Scripps Research Institute who has researched the origins of Covid-19, is more forthright about the research on which Richard Dearlove based his claim that the virus could be man-made.

“It is nonsense, unintelligible, and not even remotely scientific,” he said, adding that the authors, one of whom is a British academic, “do not appear to understand the most basic concepts of evolutionary biology.”

One conspiracy theory about the virus is that it was engineered. Viral geneticists say that’s just not true.

Professor Andersen says all the evidence suggests the virus is a natural one: “No data has been put forward suggesting otherwise, including in the present ‘study’.”

If the virus is not bioengineered, then the point about accidental escape of bat viruses is however lax biosecurity in a top security lab, who could possibly believe that biosecurity in the massive wuhan live markets is better?

The Wuhan lab story is (plausible, from a distance) fake news.

Quote from THHuxleynew

Ever heard of insertion and recombination? or looked at the table (in my other link) of matching of different critical subsequences? In any case the significance of that virus is as below. Read on...

This post (validated by two others liking it). Makes me go check the polybasic Furin cleavage argument again. Maybe Mark U is right and all those biologists are wrong? It was not as simplistic as supposed above, if you read the link I provided, which I bet mark U did not. However, I read it very quickly, so let's do a more detailed review...

https://www.virology.ws/2020/0…arginine)%20amino%20acids

The figure shows amino acids at cleavage sites in the spike glycoproteins of various CoVs. A furin site is present in the spike glycoprotein of HCoV-OC43, HCoV-HKU1, MERS-CoV and SARS-CoV 2. It is called a multibasic site because it contains multiple basic (arginine) amino acids. The spike glycoproteins of HCoV-NL63, HCoV-229E, and SARS-CoV do not contain this multibasic cleavage site. Neither do SARS-related CoVs found in bats, including RaTG13, the virus with the closest overall genome sequence identity with SARS-CoV-2.

An interesting question is the origin of the furin cleavage site it SARS-CoV-2. Its closest relative, the bat isolate RaTG13, does not have this site. Nor do any of the other bat SARS-like CoVs or the pangolin CoVs that have been isolated. However recently a newly isolated bat SARS-like CoV, RmYN02, was shown to contain a poly basic amino acid insertion in the spike glycoprotein. This observation supports the hypothesis that the furin cleavage site in SARS-CoV-2 arose by recombination among bat viruses in nature.

So the link is this: polybasic amino acid insertions happen naturally in bat viruses. Therefore the polybasic Furin cleavage site found in sars-cov-2 is an expected natural occurrence in bat viruses. Contrary to the "it must have come from a lab" argument.

Zhou et al. report a bat-derived coronavirus, RmYN02, which is the closest relative of SARS-CoV-2 in most of the virus genome reported to date. RmYN02 contains an insertion at the S1/S2 cleavage site in the spike protein in a similar manner to SARS-CoV-2. This suggests that such insertion events can occur naturally in animal betacoronaviruses.

THH

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Oh I read it alright. But I did more and read the paper it referenced at cell.com. Nowhere in the cell.com paper does it say that RMYN02 has a poly basic insertion in the spike protein. Only that it's an insertion. So, the quote from the article you included, namely

"RmYN02, was shown to contain a poly basic amino acid insertion in the spike glycoprotein."

is simply false, as is this conclusion the article:

"So the link is this: polybasic amino acid insertions happen naturally in bat viruses."

The question now is, why did the author say these things? Why not simply say that natural insertions are know to have happened in the spike protein of corona viruses?

No, he had to make it appear that the polybasic insertion we find in SARS CoV-2 was as natural as rain. It isn't, and the author is suspect.

About recombination. One requires homologous DNA in the area for this to occur with any reasonable probably. The problem is that, with coronaviruses that *are* homologous to SARS CoV-2 in that area, there have been found no such insertions. They are much rarer than point mutations, and they are often unstable and revert.

There are so many improbabilities involved in the existence of SARS CoV-2, that is should be a no brainer to seriously contemplate it was altered in lab. Instead, we get an over reaction against this very thing. Methinks some scientists protest too much. Make no mistake, a lot of scientists and funders around the world have much to lose if this virus is shown to be lab altered.